Sepsis is a persistent problem in hospitalized patients. In addition to surgery and antibiotics, nutritional support is often of importance in enabling recovery. Optimal nutritional support depends on an understanding of how the altered metabolic state changes the ability of septic patients to benefit from administered substrates. In this study we will focus on two important aspects of glucose metabolism in septic patients: 1) the regulation of glucose production; and 2) the ability to oxidize infused glucose. We will use stable isotopic tracers of glucose, alanine, and urea to investigate these factors in both human septic patients and normal volunteers. Septic patients will be classified on both clinical and physiological criteria as mild, moderate, or severe. The specific experiments we will perform are as follows: 1) Regulation of Glucose Production a) The basal rate of glucose production, gluconeogenesis from alanine, and urea production will be determined, as well as plasma concentrations of insulin, glucagon, and catecholamines. b) The rates of the above kinetic factors will be assessed during the infusion of somatostatin, insulin, and glucagon so that the levels of these hormones are equal in volunteers and septic patients. c) Unlabeled glucose will be infused at two rates (1 and 4 mg/kg.min) both with and without hormonal control, as described in 1(b), in order to test the suppressive effect of hyperglycemia (Plus or Minus) hyperinsulinemia on glucose production. 2) Glucose Oxidation a) We will compare the ability of septic patients to directly oxidize glucose infused at various rates with that of normal volunteers. b) The potential inhibitory effect of high FFA levels on glucose oxidation will be tested by determining glucose oxidation rates with and without added lipid infusion. Results from these studies should clarify fundamental aspects of glucose metabolism in sepsis that will be directly relevant to the administration of glucose in nutritional support.